Identification of persons truly allergic to penicillin and cephalosporin antibiotics is still a major unresolved and expensive public health problem. Existing licensed skin testing material detects less than half of persons susceptible to anaphylactic reactions to penicillin, is of no value in diagnosing hypersensitivity in non-urticarial drug associated rashes, and when positive in urticarial rashes has the effect of over-estimating the extent of cross-hypersensitivity with other penicillins and cephalosporins. A major improvement in clinical skin testing and other diagnostic materials for diagnosis of non-penicilloyl reaginic hypersensitivity will be sought by characterizing antigenically active fractions obtained by chromatography and isoelectric focusing from minor determinant solutions. Polylysines bearing sidechain-linked penicillin with nucleus modified to mimic minor determinants will be evaluated for their relevance in detecting allergy to minor determinants and compared with isolated purified MDM antigens. Studies comparing the effects of sidechain structure on immunochemically significant degradation reactions will be continued. Evidence for a cell mediated immunopathogenesis will be sought in patients experiencing non-urticarial drug rash responses and allergic interstitial nephritis reactions to beta-lactam antibiotics. A guinea pig model of cell mediated immunity (CMI) to beta-lactam antibiotics will be used to validate in vitro assays for CMI (antigen-dependent DNA synthesis; agarose leukocyte migration inhibition) and to study the mechanism and treatment of allergic interstitial nephritis. The CMI response of normal and hypersensitive humans will be compared using in vitro assays, and evidence will be sought for tolerogenic and suppressor mechanisms. Diagnostic testing systems that are practical and clinically useful as well as new information on mechanisms of reactions and potential modes of desensitization will result from these studies on penicillin allergy.